2026-04-14T17:43:22Zhttps://uvadoc.uva.es/oai/requestoai:uvadoc.uva.es:10324/714642024-12-11T10:53:05Zcom_10324_1138com_10324_931com_10324_894col_10324_1226
Di Pierdomenico, Johnny
Gallego-Ortega, Alejandro
Norte-Muñoz, María
Vidal-Villegas, Beatriz
Bravo, Isaac
Boluda-Ruiz, María
Bernal-Garro, Jose Manuel
Fernández Bueno, Iván
Pastor Jimeno, José Carlos
Villegas-Pérez, María Paz
Avilés-Trigueros, Marcelino
de los Ríos, Cristobal
Vidal Sanz, Manuel Antón
2024-11-14T12:14:36Z
2024-11-14T12:14:36Z
2024
Frontiers in Neuroanatomy 2024;18
https://uvadoc.uva.es/handle/10324/71464
10.3389/fnana.2024.1335176
Frontiers in Neuroanatomy
18
1662-5129
Producción Científica
Purpose: The aim of this study was to investigate, the neuroprotective effects of
a new Gramine derivative named: ITH12657, in a model of retinal excitotoxicity
induced by intravitreal injection of NMDA.
Methods: Adult Sprague Dawley rats received an intravitreal injection of 100 mM
NMDA in their left eye and were treated daily with subcutaneous injections of
ITH12657 or vehicle. The best dose–response, therapeutic window study, and
optimal treatment duration of ITH12657 were studied. Based on the best survival of
Brn3a + RGCs obtained from the above-mentioned studies, the protective effects of
ITH12657 were studied in vivo (retinal thickness and full-field Electroretinography),
and ex vivo by quantifying the surviving population of Brn3a + RGCs, αRGCs and
their subtypes α-ONsRGCs, α-ONtRGCs, and α-OFFRGCs.
Results: Administration of 10 mg/kg ITH12657, starting 12 h before NMDA
injection and dispensed for 3 days, resulted in the best significant protection
of Brn3a + RGCs against NMDA-induced excitotoxicity. In vivo, ITH12657-
treated rats showed significant preservation of retinal thickness and functional
protection against NMDA-induced retinal excitotoxicity. Ex vivo results showed
that ITH12657 afforded a significant protection against NMDA-induced
excitotoxicity for the populations of Brn3a + RGC, αRGC, and αONs-RGC, but
not for the population of αOFF-RGC, while the population of α-ONtRGC was
fully resistant to NMDA-induced excitotoxicity.
Conclusion: Subcutaneous administration of ITH12657 at 10 mg/kg, initiated
12 h before NMDA-induced retinal injury and continued for 3 days, resulted in the
best protection of Brn3a + RGCs, αRGC, and αONs-RGC against excitotoxicity-
induced RGC death. The population of αOFF-RGCs was extremely sensitive
while α-ONtRGCs were fully resistant to NMDA-induced excitotoxicity.
PID2019-106498GB-I00 funded by Ministerio de Ciencia, Innovación y Universidades (MCIN)/AEI/ 10.13039/501100 011033 to MV-S and MA-T; (RetiBrain) RED2018-102499-T to MV-S; and by the Instituto de Salud Carlos III (PI19/01724 to CdlR) and co-funded with the European Regional Development Fund (ERDF) within the “Plan Estatal de Investigación Científica y Técnica y de Innovación 2017–2020” (FIS/PI 18–00754) to MV-P
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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Evaluation of the neuroprotective efficacy of the gramine derivative ITH12657 against NMDA-induced excitotoxicity in the rat retina
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